A Few Additional Sirtris Links

I thought I'd point out a couple of links of interest to those following the recent burst of news on resveratrol and the efforts of Sirtris Pharmaceuticals. First out of the gate, an interview with David Sinclair (co-founder of Sirtris) by Charlie Rose can be found at Google Video. From Sinclair's Harvard faculty page:

Our goal is to devise ways to prevent and treat the major diseases of society by manipulating genes that control how fast we age. ... These genes underlie the remarkable effects of the diet known as calorie restriction (CR), which delays aging in every species tested, from yeast to primates. CR is currently the only treatment that can prevent all diseases of aging including cancer, heart disease, osteoporosis, diabetes and neurodegeneration. Recent studies in our lab and others demonstrate that the ability of CR to extend lifespan in models organisms is governed by the Sirtuins. Animals lacking Sirtuin genes do not respond to CR and additional gene copies extend lifespan. Based on these findings, we have engineered small molecules that can activate mammalian Sirtuins in vivo, with a view to developing drugs that can (i) treat the diseases of aging and (ii) promote cell survival and recovery following an injury.

This is one of the most representative and advanced efforts of that segment of the research community presently attempting to safely change metabolism to slow aging. Unfortunately, given that the FDA will not approve any treatment for aging itself, these sorts of efforts are channeled into developing treatments for specific age-related conditions - the short-termist and ultimately ineffective process of patching up the consequences of aging, with no impetus to commercialize preventative methodologies. This is not good: you get things done by getting things done. If you're not working on A, you're not working on A, even if you're working on B that is related to A. Regulation in the US steers research investment and infrastructure away from making any serious effort to repair or prevent aging. This must change.

The present day mainstream approach to age-related degeneration, disease and frailty is a function and outgrowth of a historical lack of knowledge; if you don't know why the dam is crumbling, you get to plugging the holes and damn the expense. When plugging the holes is all you can do, then it's all you can do - it'll cost the moon and the dam will collapse only a little later than it would otherwise have done.

We can do better than this. Not right now, but soon.

But back to Sirtris and their present work:

Elixir and Sirtris:

So researchers are developing drugs to treat or prevent aging-related diseases like diabetes or obesity. The current explosion of anti-aging research dates to the 1930s when scientists discovered that dramatically reducing an animal's caloric intake will pile on extra years. ... Sirtris researchers have developed small molecules aimed at triggering the health-promoting effects from caloric restriction found in sirtuins, a class of enzymes. Elixir is also researching sirtuins, but it's seeking ways to treat diabetes and obesity by targeting ghrelin, a protein released in the stomach that regulates hunger and metabolic functions."

Press Release on Sitris' SRT501:

Sirtris Pharmaceuticals, the leading sirtuin therapeutics company, announced today that SRT501, its initial clinical candidate which is a proprietary formulation of resveratrol with improved bioavailability, has been administered to patients with Type 2 diabetes in a human Phase 1b clinical study. Sirtris is studying SRT501 as a drug candidate for Type 2 diabetes, based in part on the scientific evidence that sirtuin activation, by means of compounds like resveratrol, has been shown to have a positive effect on key clinical measures for diabetes.

Lastly, a teaser via Pimm and Chris Patil suggests there are more interesting attempts at metabolic manipulation to come:

I think the first really useful technological life extension will have a very familiar form, e.g., “take this pill and call me in fifty years when you’re still alive.” Drugs that activate sirtuins and related pathways are very promising (I can’t spill the beans but I saw some amazing data at Cold Spring Harbor suggesting that there are already several working drugs). Once we’re better able to get our brains around calorie restriction, I think that CR mimetics will be right behind the sirtuin-based drugs. To the extent that these sorts of drugs will help prevent acknowledged illnesses like Type II diabetes, there’s already a clinical indication for them, so they should sail through approval on that basis.

Like it or not, the main thrust of the research community interesting in healthy longevity is presently towards metabolic manipulation and slowing aging. If we want better ways forward - fixing age-related damage, rejuvenation and reversing aging - to gain greater funding and come to dominate, we're going to have to prove our case.

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